反应详情

温度

110 °C

A solution of 1.0 g (2.95 mmol) 6-chloro-2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-pyridine-3-carboxylic acid amide (synthesis is described in section b) of example 2) in propionitrile (20 ml) was treated with 1.33 g (8.87 mmol) NaI and 1.0 ml (8.28 mmol) trichloromethylsilane. Subsequently the solution was heated at 110° C. for 16 h. The mixture was then partitionated between a 2M aq. NaOH sol and EtOAc. The organic layer was separated, washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in dioxane (10 ml) and 2.26 g (7.0 mmol) Cs2CO3 and 114 mg (0.92 mmol) picolinic acid were added. This mixture was degassed for 30 min followed by the addition of 88 mg (0.46 mmol) CuI and 470 mg (4.65 mmol) 3-morpholinone. The reaction solution was then heated to 100° C. for 16 h and subsequently concentrated in vacuo. The residue was dissolved in water and was extracted with EtOAc. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 7:3) provided 60 mg (0.15 mmol, 5%) 2-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-6-(3-oxo-morpholin-4-yl)-pyridine-3-carboxylic acid amide (example 312). [M+H]+ 404.1.

1. customThe organic layer was separated
2. washwashed with brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated in vacuo
5. dissolutionThe residue was dissolved in dioxane (10 ml)
6. customThis mixture was degassed for 30 min
7. temperatureThe reaction solution was then heated to 100° C. for 16 h
8. concentrationsubsequently concentrated in vacuo
9. dissolutionThe residue was dissolved in water
10. extractionwas extracted with EtOAc
11. washThe organic layer was washed with water and brine
12. dry with materialdried over Na2SO4
13. concentrationconcentrated in vacuo
14. customPurification of the residue by CC (hexane/EtOAc 7:3)